ESPE Abstracts

Objective: This study aim ed to report four Chinese patients due to FBN1 mutations including one with geleophysic dysplasia (GD) and three with acromicric dysplasia (AD), and analyze the clinical and genetic features of all Chinese patients.

Methods: The clinical features, laboratory tests and gene mutations of four Chinese patients with GD and AD were reported, and literatures were reviewed to analyze the clinical and genetic features of all Chinese cases retrospectively.

Results: The four children were seven years and one month old, two years and six months old, nine years and one month old, and five years and eight months old when referred to our clinic, respectively, including three boys and one girl. The clinical manifestation presented severe short stature, short limbs, delayed bone age, joint limitations, skin thickness, facial dysmorphism, hepatomegaly, pulmonary stenosis, and repeated respiratory infections. Four heterozygous missense variants of FBN1 were identified including three reported variants and one novel variant c.5159G>C. Case 1 was once treated by recombinant human growth hormone (rhGH) for one year, and the height velocity was 5cm/y. Case 1 was followed up to 14 years old, with a height of 130cm (HtSDS -5.34). Case 2 was followed up to seven years and ten months old, with a height of 89cm (HtSDS -7.26). Counting our four patients, there were total 38 Chinese cases coming from 25 different families reported, including 15 individuals with GD and 23 individuals with AD. All the cases presented severe short stature, and most showed short limbs, joint limitations, facial dysmorphism and delayed bone age. Compared to other races, skin thickness was more common and respiratory disease was less common in Chinese patients. The most common variant in Chinese cases was c.5284G>A. The same genotype can be clinically manifested as GD or AD.

Conclusion: Heterogeneity of clinical manifestations was showed in Chinese patient with FBN1 -related GD and AD. Severe short stature was the most important clinical presentation, and other common features included short limbs, joint limitations, skin thickness, facial dysmorphism, delayed bone age, hepatomegaly and cardiac involvement. The most common variant in Chinese cases was c.5284G>A. Further studies with larger samples and comparisons with other races are necessary to clarify the possible racial variability and genotype-phenotype correlation in Chinese patients.